Lisinopril Organica (Tablets) Instructions for Use

Marketing Authorization Holder

Organika, JSC (Russia)

ATC Code

C09AA03 (Lisinopril)

Active Substance

Lisinopril (Rec.INN)

Dosage Forms

	Lisinopril Organica	Tablets 5 mg: 20, 30 or 50 pcs.
		Tablets 10 mg: 20, 30 or 50 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, flat-cylindrical.

Excipients: calcium hydrogen phosphate dihydrate 0.075 g, corn starch 0.02 g, lactose monohydrate 0.0724 g, povidone 0.0016 g, talc 0.0045 g, calcium stearate 0.0015 g.

10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
20 pcs. – jars (1) of light-protective glass – cardboard packs.
30 pcs. – jars (1) of light-protective glass – cardboard packs.
50 pcs. – jars (1) of light-protective glass – cardboard packs.

Tablets white or almost white, biconvex.

Excipients: calcium hydrogen phosphate dihydrate 0.1 g, corn starch 0.025 g, lactose monohydrate 0.0744 g, povidone 0.0022 g, talc 0.0063 g, calcium stearate 0.0021 g.

10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
20 pcs. – jars (1) of light-protective glass – cardboard packs.
30 pcs. – jars (1) of light-protective glass – cardboard packs.
50 pcs. – jars (1) of light-protective glass – cardboard packs.

Clinical-Pharmacological Group

ACE inhibitor

Pharmacotherapeutic Group

Agents acting on the renin-angiotensin system; angiotensin-converting enzyme (ACE) inhibitors

Pharmacological Action

An angiotensin-converting enzyme (ACE) inhibitor, it reduces the formation of angiotensin II from angiotensin I. The decrease in angiotensin II content leads to a direct reduction in aldosterone secretion. It reduces the degradation of bradykinin and increases the synthesis of prostaglandins. It reduces total peripheral vascular resistance, blood pressure, preload, pulmonary capillary wedge pressure, causes an increase in cardiac output and improves myocardial tolerance to stress in patients with chronic heart failure. It dilates arteries to a greater extent than veins. Some effects are explained by the impact on the tissue renin-angiotensin-aldosterone system. With long-term use, it reduces hypertrophy of the myocardium and walls of resistive arteries. It improves blood supply to the ischemic myocardium. In addition to lowering blood pressure, Lisinopril Organica reduces albuminuria.

ACE inhibitors prolong the life expectancy of patients with chronic heart failure and slow the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure.

The onset of action is within 1 hour. The maximum effect is determined after 6-7 hours, duration is 24 hours. In arterial hypertension, the effect is noted in the first days after the start of treatment, a stable effect develops after 1-2 months.

Pharmacokinetics

Absorption – 30% (6-60%); bioavailability – 25%. It is weakly bound to plasma proteins. Permeability through the blood-brain barrier and placental barrier is low. The C_max of Lisinopril Organica in blood plasma is 90 ng/ml. The time required to reach C_max is 7 hours.

It is practically not metabolized and is excreted by the kidneys unchanged. T_1/2 is 12 hours.

In patients with chronic heart failure, the absorption and clearance of Lisinopril Organica are reduced.

In patients with renal insufficiency, the concentration of Lisinopril Organica is several times higher than the concentrations in the blood plasma of volunteers, and an increase in the time to reach C_max in plasma and an increase in T_1/2 are noted.

In elderly patients, the plasma concentration of the drug and the area under the curve are 2 times greater than in young patients.

Indications

• Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);
• Chronic heart failure (as part of combination therapy for the treatment of patients taking cardiac glycosides and/or diuretics);
• Early treatment of acute myocardial infarction as part of combination therapy (within the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevent left ventricular dysfunction and heart failure);
• Diabetic nephropathy (reduction of albuminuria in patients with type 1 diabetes with normal blood pressure and patients with type 2 diabetes with arterial hypertension).

ICD codes

Dosage Regimen

Orally, once a day in the morning, regardless of meals, preferably at the same time.

For arterial hypertension in patients not receiving other antihypertensive agents, 5 mg once a day is used. If there is no effect, the dose is increased every 2-3 days by 5 mg to an average therapeutic dose of 20-40 mg/day (increasing the dose above 40 mg/day usually does not lead to a further decrease in blood pressure). The usual daily maintenance dose is 20 mg. The maximum daily dose is 40 mg. If the therapeutic effect is insufficient, it is possible to combine the drug with other antihypertensive agents.

If the patient received prior treatment with diuretics, then the intake of such drugs must be discontinued 2-3 days before starting the use of Lisinopril Organica.

If this is not possible, then the initial dose of Lisinopril Organica should not exceed 5 mg per day. In this case, after taking the first dose, medical supervision is recommended for several hours (maximum effect is reached in about 6 hours), as a pronounced decrease in blood pressure may occur.

For renovascular hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system, it is also advisable to prescribe a low initial dose of 5 mg per day under enhanced medical supervision (control of blood pressure, renal function, serum potassium levels). The maintenance dose, while continuing strict medical supervision, should be determined depending on the dynamics of blood pressure. In renal insufficiency, since Lisinopril Organica is excreted by the kidneys, the initial dose should be determined depending on the creatinine clearance (CC). Further dose selection should be made depending on individual responses with regular monitoring of renal function, serum potassium, and sodium levels. The initial dose for CC 30-70 ml/min is 5-10 mg/day, 10-30 ml/min – 5 mg/day, less than 10 ml/min, including patients on hemodialysis – 2.5 mg/day.

For chronic heart failure: initial dose – 2.5 mg per day, with a gradual increase after 3-5 days to 5-10 mg per day. The maximum daily dose is 20 mg.

Early treatment of acute myocardial infarction (as part of combination therapy) within the first 24 hours – 5 mg, then 5 mg after one day, 10 mg after two days and then 10 mg once a day. The course of treatment is at least 6 weeks. At the beginning of treatment or within 3 days after acute myocardial infarction in patients with low systolic blood pressure (120 mm Hg or below), a lower dose of 2.5 mg is prescribed. In case of a decrease in blood pressure (systolic blood pressure below or equal to 100 mm Hg), the daily dose of 5 mg, if necessary, is reduced to 2.5 mg. In case of a prolonged pronounced decrease in blood pressure (systolic blood pressure less than 90 mm Hg for more than 1 hour), treatment with the drug should be discontinued.

For diabetic nephropathy (reduction of albuminuria in patients with type 1 diabetes with normal blood pressure and in patients with type 2 diabetes with arterial hypertension): initial dose – 10 mg/day, which, if necessary, is increased to 20 mg/day to achieve target diastolic blood pressure values.

It is possible to use lisinopril in other dosage forms – tablets 2.5 mg or tablets 5 mg with a score to provide this dosing regimen.

Adverse Reactions

The most common side effects: dizziness, headache (in 5-6% of patients), weakness, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rash, chest pain (1-3%).

Other side effects (frequency <1%)

From the immune system (0.1%) angioedema (face, upper and lower extremities, lips, tongue, larynx or epiglottis).

From the cardiovascular system palpitations, tachycardia, orthostatic hypotension, myocardial infarction, cerebrovascular stroke in patients with an increased risk of the disease due to a pronounced decrease in blood pressure, impaired renal function.

From the CNS asthenic syndrome, mood lability, confusion, increased fatigue, drowsiness, convulsive twitching of the muscles of the limbs and lips.

From the hematopoietic system leukopenia, neutropenia, agranulocytosis, thrombocytopenia are possible; with long-term treatment – a slight decrease in hemoglobin and hematocrit, erythropenia.

From the digestive tract dryness of the oral mucosa, anorexia, dyspepsia, taste changes, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

From the skin urticaria, increased sweating, skin itching, alopecia.

From the urinary system impaired renal function, oliguria, anuria, acute renal failure, uremia, proteinuria.

Laboratory parameters hyperkalemia, azotemia, hyperuricemia, hyperbilirubinemia, increased activity of liver transaminases, especially in patients with a history of kidney disease, diabetes and renovascular hypertension.

Other myalgia, fever, impaired fetal development.

Contraindications

• History of angioedema, including against the background of ACE inhibitor use;
• Hereditary angioedema or idiopathic angioedema;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
• Pregnancy;
• Lactation period;
• Age under 18 years (efficacy and safety not established);
• Hypersensitivity to Lisinopril Organica or other ACE inhibitors, other components of the drug.

With caution

Severe renal impairment; bilateral renal artery stenosis or stenosis of the artery of a single kidney with progressive azotemia; condition after kidney transplantation; renal failure, azotemia; diabetes mellitus; hyperkalemia; aortic stenosis; hypertrophic obstructive cardiomyopathy; primary hyperaldosteronism; arterial hypotension; cerebrovascular diseases (including cerebrovascular insufficiency); ischemic heart disease; coronary insufficiency; autoimmune systemic connective tissue diseases (including scleroderma, systemic lupus erythematosus); bone marrow depression; diet with salt restriction; hypovolemic conditions (including as a result of diarrhea, vomiting); elderly age.

Use in Pregnancy and Lactation

If pregnancy is established, the use of Lisinopril Organica should be discontinued as soon as possible. The use of ACE inhibitors in the II and III trimesters of pregnancy has an adverse effect on the fetus (possible pronounced decrease in blood pressure, renal failure, hyperkalemia, skull hypoplasia, intrauterine death).

There are no data on the negative effects of the drug on the fetus in case of use during the first trimester. Newborns and infants who have been exposed to ACE inhibitors in utero are recommended to be carefully monitored for the timely detection of a pronounced decrease in blood pressure, oliguria, and hyperkalemia.

Lisinopril Organica crosses the placenta. There are no data on the excretion of Lisinopril Organica into breast milk. If the use of Lisinopril Organica is necessary during lactation, breastfeeding should be discontinued.

Use in Renal Impairment

The drug should be used with caution in severe renal impairment.

Pediatric Use

Contraindication: age under 18 years (efficacy and safety not established).

Geriatric Use

The drug should be used with caution in elderly patients.

Special Precautions

Symptomatic hypotension: most often, a pronounced decrease in blood pressure occurs with a decrease in circulating blood volume (CBV) caused by diuretic therapy, reduced salt in the diet, dialysis, diarrhea or vomiting. In patients with chronic heart failure with or without concomitant renal insufficiency, a pronounced decrease in blood pressure is possible. Lisinopril Organica should be used under strict medical supervision in patients with coronary artery disease, cerebrovascular insufficiency, in whom a sharp decrease in blood pressure can lead to myocardial infarction or stroke.

Transient arterial hypotension is not a contraindication for taking the next dose of the drug.

When using Lisinopril Organica, in some patients with chronic heart failure but with normal or reduced blood pressure, a decrease in blood pressure may be noted, which is usually not a reason to discontinue treatment.

Before starting treatment with the drug, if possible, the sodium content should be normalized and/or the CBV should be replenished, and the effect of the initial dose of Lisinopril Organica on the patient should be carefully monitored.

In the case of renal artery stenosis (especially with bilateral stenosis or with stenosis of the artery of a single kidney), as well as in circulatory insufficiency due to a lack of sodium ions and/or fluid, the use of Lisinopril Organica may lead to impaired renal function, acute renal failure, which is usually irreversible even after drug withdrawal.

In acute myocardial infarction, the use of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers) is indicated. Lisinopril Organica can be used in conjunction with intravenous administration or with the use of therapeutic transdermal nitroglycerin systems.

Surgical intervention/general anesthesia: during extensive surgical interventions, as well as when using other agents that cause a decrease in blood pressure, Lisinopril Organica, by blocking the formation of angiotensin II, can cause a pronounced unpredictable decrease in blood pressure.

Angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx has been rarely observed in patients treated with ACE inhibitors, which can occur at any time during treatment. In such a case, treatment with Lisinopril Organica must be discontinued as soon as possible and the patient should be monitored until the symptoms completely regress. In cases where only the face and lips are swollen, the condition most often resolves without treatment, however, antihistamines may be prescribed.

Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis, or larynx is involved, airway obstruction may occur. Therefore, appropriate therapy should be immediately administered (0.3-0.5 ml of epinephrine (adrenaline) solution 1:1000 subcutaneously, administration of glucocorticosteroids, antihistamines) and/or measures to ensure airway patency. In patients who have a history of angioedema not associated with previous ACE inhibitor treatment, the risk of its development during ACE inhibitor treatment may be increased. An anaphylactic reaction has been noted in patients on hemodialysis using high-flux dialysis membranes (AN69^®) who are simultaneously taking ACE inhibitors. In such cases, the possibility of using another type of dialysis membrane or another antihypertensive agent should be considered. Anaphylactic reactions may occur during low-density lipoprotein apheresis with dextran sulfate. In isolated cases of desensitization to hymenoptera venom, treatment with ACE inhibitors was accompanied by hypersensitivity reactions. This can be avoided by temporarily discontinuing ACE inhibitors beforehand.

In elderly patients, the same dose leads to a higher concentration of the drug in the blood, so special caution is required when determining the dose.

Cough has been observed with the use of ACE inhibitors. The cough is dry, prolonged, and disappears after discontinuation of ACE inhibitor treatment. In the differential diagnosis of cough, cough caused by the use of ACE inhibitors should be considered.

Based on the results of epidemiological studies, it is assumed that the simultaneous use of ACE inhibitors and insulin, as well as oral hypoglycemic agents, may lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function. In patients with diabetes mellitus, careful monitoring of glycemia is required, especially during the first month of therapy with an ACE inhibitor.

In some cases, hyperkalemia has been observed. Risk factors for the development of hyperkalemia include renal failure, diabetes mellitus, the use of potassium preparations or drugs that cause an increase in blood potassium levels (e.g., heparin), especially in patients with impaired renal function. During treatment with the drug, regular monitoring of plasma potassium ions, glucose, urea, and lipids in patients is necessary.

During the treatment period, it is not recommended to consume alcoholic beverages, as alcohol enhances the hypotensive effect of the drug.

Since the potential risk of agranulocytosis cannot be excluded, periodic monitoring of the blood picture is required.

Influence on the ability to drive vehicles and mechanisms

There are no data on the effect of Lisinopril Organica on the ability to drive vehicles and mechanisms when used in therapeutic doses; however, it is necessary to consider that dizziness may occur, so caution should be exercised.

Overdose

Symptoms pronounced decrease in blood pressure, dryness of the oral mucosa, disturbance of water-electrolyte balance, renal failure, increased respiration rate, tachycardia, sensation of palpitations, bradycardia, dizziness, anxiety, increased irritability, cough, drowsiness, urinary retention, constipation.

Treatment symptomatic therapy, intravenous administration of a 0.9% sodium chloride solution, if necessary – vasopressor drugs, monitoring of blood pressure and water-electrolyte balance. Hemodialysis is effective. Gastric lavage, use of enterosorbents and laxatives. In case of persistent bradycardia, the placement of a temporary pacemaker is necessary.

Drug Interactions

Slows the excretion of lithium preparations (the excretion of lithium may decrease, so the serum lithium concentration should be regularly monitored).

Nonsteroidal anti-inflammatory drugs (including selective cyclooxygenase-2 inhibitors), estrogens, and adrenergic stimulants reduce the hypotensive effect.

Simultaneous use with potassium-sparing diuretics and potassium preparations may lead to hyperkalemia.

Combined use with beta-blockers, slow calcium channel blockers, diuretics, tricyclic antidepressants/antipsychotics, and other antihypertensive drugs increases the severity of the hypotensive effect.

Antacids and cholestyramine reduce absorption in the gastrointestinal tract and decrease the hypotensive effect of Lisinopril Organica.

Agents with myelosuppressive action, when used concomitantly with Lisinopril Organica, increase the risk of developing neutropenia and/or agranulocytosis.

Allopurinol, cytostatics, immunosuppressants, procainamide when used concomitantly with Lisinopril Organica may lead to the development of leukopenia; in addition, allopurinol and procainamide in combination with Lisinopril Organica may lead to the development of erythema multiforme.

With the simultaneous use of ACE inhibitors and intravenous gold preparations (sodium aurothiomalate), a symptom complex including facial flushing, nausea, vomiting, and decreased blood pressure has been described.

Concomitant use with selective serotonin reuptake inhibitors may lead to severe hyponatremia.

Concomitant use with insulin and oral hypoglycemic agents may increase the risk of developing hypoglycemia.

A case of severe hyperkalemia has been described in a patient with diabetes mellitus with simultaneous use with lovastatin.

A case of severe arterial hypotension has been described with simultaneous use with pergolide.

Lisinopril Organica enhances the manifestations of alcohol intoxication. Against the background of alcohol consumption, an enhancement of the hypotensive effect of Lisinopril Organica is possible.

Narcotic analgesics, anesthetics, hypnotics in combination with Lisinopril Organica cause an enhancement of the hypotensive effect.

The antihypertensive effect of Lisinopril Organica is reduced against the background of excessive consumption of sodium chloride.

Storage Conditions

Store in a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of the reach of children.

Shelf Life

The shelf life is 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.